RefG Heart Development co-curation

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Title of Project: Heart Development co-curation

Lead group, lead curator

BHF-UCL group, Varsha Khodiyar; Cardiovascular GO annotation initiative

Reference Genome Start Date Preference

May 2011

Number of proposed targets

60 in full list (36 human transcription factor targets)

Short description to background of proposed project

The recent ontology workshop on heart development terms means that the ontology to support the annotation of this set of genes already exists.

The heart is interesting from an evolutionary standpoint, for example fish have a 4-chambered heart, with the chambers arranged in a sequential manner, and frogs have a 3-chambered heart. Therefore it will be interesting to see how the functions of the gene products change across species.


The heart is also of interest from the viewpoint of human health. There are many model organisms used to study the heart and this project will help to annotate the gene products of organisms that are important to cardiovascular research, but are not reference genome species, for example the dog.


The target list is rich in proteins involved in a number of central signaling pathways, TGF-beta and Wnt-catenin signaling for example. Thus, the annotation of this set will also serve as a through test and aid ongoing improvements of the new signaling ontology. However the current project (May-September 2011) will focus on just the transcription factors that are involved in heart development to take advantage of the recent work on the transcription ontology.

Description of original target selection

During the heart development workshop, the heart experts were asked for their opinions as to which genes were important in specific developmental processes. This list was combined with literature reviews to generate further genes of interest. This set was sent back to the heart experts for review and 4 of their additional suggestions were incorporated. Additionally, 18 targets have been included for which the only evidence gathered is that the mouse ortholog has been annotated with one (or more) of the following mammalian phenotype terms:

  • MP:0003974 - abnormal endocardium morphology
  • MP:0008825 - abnormal cardiac epithelial to mesenchymal transition
  • MP:0004252 - abnormal direction of looping morphogenesis

It expected that as annotation proceeds, the literature will further support the inclusion of these targets in the heart development set.

There are a number of other mammalian phenotype terms which are relevant to heart development, but which have not been selected in this target set. The reason is that the aim was to generate a list of only 60 panther families. However, as the annotation proceeds it is likely that additional targets will become obvious, the annotation of which would help the heart development annotation set to feel more complete. So if possible, it is suggested that the option of adding an extra month to the project would be beneficial. This would allow time for the annotation of new targets that have come out of the initial 3-month project.

From this original target list, 36 human proteins believed to act as transcription factors have been selected.


Previous reference genome targets

The initial heart development set from the experts included 24 previous reference genome targets. Of these, seven were ref genome targets prior to May 09 and so it is felt that they will benefit from further annotation with the updated ontology. The remaining 17 were in the mouse lung target set. Of these only 3 of the human genes are fully annotated at the time of writing. The remaining 14 require annotation both for the mouse lung project and the heart development project. It is suggested these 14 targets are given the highest possible priority, as they are important for both the mouse lung project and heart development. However, as they had been selected previously they are not included in the set of 60 heart development targets.


Limitations of target set

The Panther subfamily has been specified where possible in order to minimize the number of non-heart development related proteins included in each family. Where there are multiple targets within a panther group, the family member specifically shown to be involved in heart development will be highlighted on the wiki as a higher priority than other non-heart development related family members. Many of the proposed targets may not be represented by orthologues in non-chordate species. Therefore an alternative set of targets may need to be found for Reference Genome groups annotating to non-chordate species.


Reference Genome Annotation Plans

This wiki page will act as a central resource for the project and will be used to help monitoring annotation progress. The attached discussion page will be used to highlight interesting points/difficulties, and capture any data that could be considered for publication purposes.


Ideas for annotation data exploitation

The annotations will be analyzed at the end of the project, to see if GO annotations can highlight the functional differences between species. Ongoing contact with heart development experts will be maintained to seek additional value for the project.


Heart Development Review Papers

  1. PMID: 19647421 Protein interactions at the heart of cardiac chamber formation

Review of the heart across species.

  1. PMID: 19592411 'And the beat goes on.' The cardiac conduction system: the wiring system of the heart.

Review of cardiac conduction system development

  1. PMID: 19390062 Signaling pathways controlling second heart field development

Review of signaling in second heart field development

  1. PMID: 19371733 Shaping the zebrafish heart: from left-right axis specification to epithelial tissue morphogenesis

Review of zebrafish heart development

  1. PMID: 17098821 Another key role for the cardiac neural crest in heart development

Neural crest cell contribution to heart development

  1. PMID: 20186050 The molecular genetics of congenital heart disease: a review of recent developments

Review of transcription factors involved in heart development

  1. PMID: 20201901 Developmental basis of adult cardiovascular diseases

EMT contribution to heart valve development

RG electronic jamboree

Use this page to collect examples for discussion at the Reference Genome jamboree on Transcription http://gocwiki.geneontology.org/index.php/Transcription_jamboree


Heart Development Transcription Annotation Targets

Annotation period (week beginning) Panther Families Gene Symbol of representative family members (Human protein ID) PAINT due to begin GOA / BHF-UCL MGI RGD ZFIN Wormbase Flybase Agbase Dictybase TAIR SGD Pombase
Week 1 (9th May 2011) PTHR10071 GATA4 (P43694) priority genes done done done done elt-1 - done no priority genes no priority genes done no priority genes no priority genes
Week 2-3 (16th May 2011) PTHR10032, PTHR24338 OVOL2 (Q9BRP0), MSX1 (P28360) priority genes done done done done hbl-1 - done no priority genes no priority genes no priority genes no priority genes
Week 4 (31st May) PTHR10270 SOX17 (Q9H6I2) priority genes done done done done sox-3 - done no priority genes no priority genes no priority genes no priority genes no priority genes
Week 5 (7th June) PTHR10985, PTHR22793 HEY2 (Q9UBP5), MYCD (Q8IZQ8) priority genes done done done done lin-22 - done no priority genes no priority genes no priority genes no priority genes
Week 6-7 (14th June) PTHR11267, PTHR23349 TBX3 (O15119), HAND2 (P61296) priority genes done 6/9 done done done tbx-2 done no priority genes no priority genes no priority genes no priority genes
Week 8 (28th June) PTHR11309, PTHR10812 SMO (Q99835), TFAP2A (P05549) priority genes done 1/2 done done done F28C6.1 - done, F28C6.2 - done no priority genes no priority genes no priority genes no priority genes
Week 9 (5th July) PTHR11389 SNAI2 (O43623) priority genes done done done done ces-1 - done no priority genes done
Week 10-11 (12th July) PTHR11945 MEF2C (Q06413) priority genes done done done done mef-2 - done no priority genes no priority genes
Week 12-13 (26th July) PTHR11829, PTHR24340 FOXA2 (Q9Y261), NKX2-5 (P52952) priority genes done done done pha-4 - done FOXA2 not a priority gene no priority genes no priority genes no priority genes no priority genes
Week 14 (2nd August) PTHR12198, PTHR24126 PROX1 (Q92786), ANKR1 (Q15327) priority genes done 1/2 done done done ceh-26 - done no priority genes no priority genes no priority genes no priority genes
Week 15 (9th August) PTHR12881, PTHR12958 MED1 (Q15648), FOG1 (Q8IX07) FOG1 done done done done no priority genes done no priority genes no priority genes no priority genes no priority genes
Week 16 (16th August) PTHR13844, PTHR23341 SMARCD3 (Q6STE5), HMGA2 (P52926) priority genes done done done done swsn-2.1 - done, swsn-2.2 - done, T24G10.2 - done CG1240 done SMARCD3 done snf12 - no papers no priority genes
Week 17 (23rd August) PTHR13864, PTHR17045 TAL1 (P17542), CITED2(Q99967) priority genes done done done hlh-15 - done no priority genes no priority genes no priority genes no priority genes
Week 18 (30th August) PTHR23043 HIF1A (Q16665) priority genes done done done no priority genes no priority genes no priority genes no priority genes no priority genes no priority genes
Week 19 (6th September) PTHR24204 ISL1 (P61371) priority genes done done done lim-7 - done tup done no priority genes no priority genes no priority genes no priority genes
Week 20 (13th September 2011) PTHR24329 PITX2 (Q99697) priority genes done done done done unc-30 - done Ptx1 done no priority genes no priority genes no priority genes no priority genes

Curation notes

1. Comprehensively annotate all the priority genes for your species in the PANTHER families listed for that week. Not all MODs will have priority genes in every family. Some MODs will have more than one priority gene in a single family. Write 'done' in relevant row of the table above, once all the priority genes have been annotated.

2. Annotate as many other members of the weekly PANTHER family as possible. Do not worry if all non-priority members of PANTHER family could not be completed within the time frame.

3. Try to move onto the next week's targets at about the dates listed above, to enable simultaneous discussion of genes/ontology developments across MODs.


Original Annotation Targets

Panther Family Gene Symbol (Human protein ID) Human protein ID Heart Development stage General process Support for Role in heart development
1 PTHR10568:SF4 DKK1 (O94907) O94907 Specification of cardiac precursor cells Wnt/beta-catenin pathway PMID: 18297060
2 PTHR20937:SF2 MESP2 (Q0VG99) Q9BRJ9 Q0VG99 Specification of cardiac precursor cells Wnt/beta-catenin pathway PMID: 11369261 | MP:0008825 | PMID: 10887078
3 PTHR24204:SF26 ISL1 (P61371) P61371 Specification of cardiac precursor cells PMID: 19571884 PMID: 17519333
4 PTHR11267:SF15 T (O15178); brachyury O15178 Specification of cardiac precursor cells Transcription factor PMID: 18767184
5 PTHR22793:SF4 MYOCD (Q8IZQ8) Q8IZQ8 Specification of cardiac muscle cells regulation of smooth muscle gene expression PMID: 15907818 Heart experts
6 PTHR11945:SF24 PTHR11945:SF46 MEF2A (Q02078) Q02078 Cardiac muscle cell specification Transcription factor PMID: 10458488 | PMID: 11316766 | PMID: 16469744
7 PTHR18973:SF26 ISL1 (P61371) P61371 Expressed by cardiac progenitor cells Beta-catenin signaling Hedgehog-smoothened signaling PMID: 17519333
8 PTHR23349:SF3 HAND1 (O96004); eHAND O96004 Ventricular morphogenesis Transcription factor PMID: 19586923 | PMID: 18276607
9 PTHR12198:SF0 PROX1 (Q92786) Q92786 Cardiomyocyte morphogenesis Transcription factor PMID:19091769
10 PTHR11945:SF25 MEF2C (Q06413) Q06413 Myocardium development Transcription factor PMID: 19899118
11 PTHR22824:SF3 AKAP13 (Q12802) Q12802 Myocardium development Kinase signaling PMID: 20139090
12 PTHR11878:SF6 SLC8A1 (P32418) P32418 Sodium ion transport MP:0003974
13 PTHR13703:SF20 SMAD6 (O43541) O43541 TGF-beta signaling MP:0003974
14 PTHR10032:SF32 OVOL2 (Q9BRP0) Q9BRP0 Seems to have a role in development in general, but is on BHF list Notch signaling MP:0003974
15 PTHR23341:SF2 HMGA2 (P52926) P52926 Cardiomyocyte differentiation Regulation of NKX2.5 transcription PMID: 18425117
16 PTHR12027:SF7 WNT11 (O96014) O96014 Cardiovascular progenitor cells Beta-catenin signaling PMID: 17519333
17 PTHR23349:SF19 HAND2 (P61296); dHAND P61296 Cardiac muscle cell differentiation Transcription factor PMID: 20144608 | PMID: 19607825
18 PTHR11036:SF11 SEMA6D (Q8NFY4) Q8NFY4 Cardiac cell migration semaphorin-plexin signaling pathway PMID: 14977921
19 PTHR22625:SF13 PLXNA1 (Q9UIW2) Q9UIW2 Cardiac cell migration semaphorin-plexin signaling pathway PMID: 14977921
20 PTHR19134:SF64 PTPN11 (Q06124) Q06124 MP:0008825
21 No panther family? C2CD3 (Q4AC94) Q4AC94 MP:0004252
22 PTHR14949:SF1 CFC1 (Q9GZR3) Q9GZR3 MP:0004252
23 PTHR10494:SF2 NOG (Q13253); Noggin Q13253 BMP inhibition MP:0004252
24 PTHR11339:SF39 CHRD (Q9H2X0) Q9H2X0 MP:0004252
25 PTHR16186:SF1 DAND5 (Q8N907) Q8N907 MP:0004252
26 PTHR10676:SF17 DYNC2H1 (Q8NCM8) Q8NCM8 MP:0004252
27 PTHR13236 DYNC2LI1 (Q8TCX1) Q8TCX1 MP:0004252
28 PTHR10795:SF3 FURIN (P09958) P09958 MP:0004252
29 PTHR10878:SF8 DVL2 (O14641) O14641 MP:0004252
30 PTHR19264:SF69 EDNRB (P24530) P24530 MP:0004252
31 PTHR11984:SF5 GJC1 (P36383) P36383 MP:0004252
32 PTHR11304:SF18 EFNB2 (P52799) P52799 MP:0004252
33 PTHR13831 HIRA (P54198) P54198 MP:0004252
34 PTHR15722:SF2 IFT172 (Q9UG01) Q9UG01 MP:0004252
35 PTHR14066:SF3 NPPA (P01160); ANF P01160 Heart chamber marker natriuretic peptide family PMID: 2522772 | PMID: 2147704
36 PTHR10812:SF8 TFAP2 (P05549) P05549 Heart morphogenesis Transcription factor PMID: 18275040 | PMID: 14975722
37 PTHR11267:SF26 TBX20 (Q9UMR3) Q9UMR3 Heart morphogenesis Transcription factor PMID: 18834961 | PMID: 17668378 | Heart experts
38 PTHR11389:SF375 SNAI1 (O95863) O95863 Cardiac cushion morphogenesis Epithelial-to-mesenchymal transition (EMT) PMID: 18663143
39 PTHR23349:SF6 TWIST1 (Q15672) Q15672 Cardiac neural crest morphogenesis Epithelial-to-mesenchymal transition (EMT) PMID: 18539270
40 PTHR11848:SF58 NODAL (Q96S42) Q96S42 Left/right patterning BMP signaling PMID: 19064609
41 PTHR17045:SF2 CITED2 (Q99967) Q99967 Left/right patterning Heart morphogenesis, specifically cardiac septal defects PMID: 15750185 | MP:0004252
42 PTHR24329:SF179 PITX2 (Q99697) Q99697 Left/right patterning Wnt/beta-catenin pathway PMID: 12464179
43 PTHR11309:SF35 SMO (Q99835) Q99835 Left/right patterning Hedgehog-smoothened signaling PMID: 16687132 | PMID: 11517919
44 PTHR11889:SF17 IHH (Q14623) Q14623 Left/right patterning Hedgehog-smoothened signaling PMID: 11517919
45 PTHR11201:SF220 DLL1 (O00548) O00548 Left/right patterning Regulation of transcription, Notch signaling MP:0004252
46 PTHR11829:SF1 FOXA2 (Q9Y261); HNF-3 beta Q9Y261 Possible roles in left/right patterning and heart looping Regulation of transcription PMID: 12062060 | MP:0004252
47 PTHR12958 ZFPM1 (Q8IX07); FOG1 Q8IX07 Heart looping Transcription factor? PMID: 14614148
48 PTHR11945:SF32 SRF (P11831); serum response factor P11831 Heart looping Transcription factor PMID: 15492011 | Heart experts
49 PTHR10799:SF70 CHD7 (Q9P2D1) Q9P2D1 Seems to have a role in development in general, but is on BHF list. DNA helicase? PMID: 17661815 | Heart experts
50 PTHR12881:SF2 MED1 (Q15648) Q15648 Seems to have a role in development in general, but is on BHF list Brings transcription factor (GATA1) and RNA pol II together PMID: 17132730
51 PTHR10373:SF11 LEF1 (Q9UJU2) Q9UJU2 Cannot find evidence of heart development role. But is on BHF list and came up in PMID:18593560 microarray analysis Wnt signalling, transcription factor PMID: 18579517
52 PTHR24338:SF137 MSX2 (P35548) P35548 Atrioventricular myocardium and AV valve formation BMP signaling, Notch signaling PMID: 18667074
53 PTHR10985:SF9 HEY2 (Q9UBP5); HESR2 Q9UBP5 Ventricular septation, blood vessel development Notch signaling PMID: 16165016
54 PTHR24247:SF85 HTR2B (P41595) P41595 Possible role in heart valve development ErbB-2 receptor signaling PMID: 11728882 | PMID: 18511249
55 PTHR24838:SF73 NOTCH1 (P46531) P46531 Left ventricle development Epithelial-to-mesenchymal transition (EMT) PMID: 18593716
56 PTHR12365 SPRY1 (O43609) O43609 Outflow tract development ERK cascade PMID: 15306693
57 PTHR23043:SF7 HIF1A (Q16665) Q16665 Angiogenesis Epithelial-to-mesenchymal transition (EMT) PMID: 19491109 | MP:0004252
58 PTHR13844 SMARCD3 (Q6STE5); Baf60c Q6STE5 Left/right patterning Notch signaling PMID: 17210915 | PMID: 15525990 | Heart experts
59 PTHR18958:SF179 ANKRD1 (Q15327) Q15327 myofibrillar stretch-sensor system Regulation of transcription PMID: 19299913 | PMID: 18956313
60 PTHR11267:SF20 TBX18 (O95935) O95935 Cardiac conduction system development Transcription factor PMID: 19213963